Pyridine, 3-bromo synthesis

Imidazo[l,2-n]pyridine, 8-amino-synthesis, 5, 631 Imidazo[l,2-n]pyridine, 3-aryl-synthesis, 5, 631-632 Imidazo[l,2-n]pyridine, 3-bromo-synthesis, 5, 631... 

Pyrazolo[ 1,5-n Jpyridine, 2-hydroxy-tautomerism, 5, 309 Pyrazolo[3,4-6]pyridine, 3-bromo-synthesis, 5, 315... 

With the catalysis of strong Lewis acids, such as tin(IV) chloride, dipyrromethenes may aiso be alkylated. A very successful porphyrin synthesis involves 5-bromo-S -bromomethyl and 5 -unsubstituted 5-methyl-dipyrromethenes. In the first alkylation step a tetrapyrrolic intermediate is formed which cyclizes to produce the porphyrin in DMSO in the presence of pyridine. This reaction sequence is useful for the synthesis of completely unsymmetrical porphyrins (K.M. Smith, 1975). 

Imidazo[4,5-c]pyridine, 6-amino-4-bromo-reactions, 5, 621 synthesis, 5, 641... 

Pyrrolo[3,4-d]pyridazinium salts, 2,3-dimethyl-synthesis, 4, 291 Pyrrolo[ 1,2-6]pyridazinones oxidation, 4, 298 Pyrrolo[2,3-6]pyridine, 1-acetyl-cycloaddition reactions, 4, 509 Pyrrolo[2,3-6]pyridine, 3-bromo-nitration, 4, 505... 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

Reaction of -picoline over degassed Raney nickel was found to give 5,5 -dimethyl-2,2 -bipyridine (5), the structure of which was established by its synthesis from 2-bromo-5-methylpyridine. Oxidation of this dimethyl-2,2 -bipyridine, and similar oxidation of the diethyl-2,2 -bipyridine derived from 3-ethylpyridinc, gave the corresponding dicarboxylic acid and the same acid was produced by the action of degassed Raney nickel on sodium nicotinate (in water) or on ethyl nicotinate. These transformations established the 5,5 -substitution pattern for three 2,2 -bipyridines derived from 3-substituted pyridines but such evidence is not available for the biaryls... 

A useful method of synthesis of 5-bromo- and 5,8-dibromo-3-methoxy-2-phenylimidazo[ 1,2-a]pyridines has involved quenching the lithium derivatives with bromine (83S987). 

Unsymmetric compartmental ligands that allow for the controlled synthesis of unsymmetric Ni2 or heterobimetallic NiM complexes have received particular attention.1876,1892 A wide range of such ligands derived particularly from 2-hydroxy-3-hydroxymethyl-5-methylbenzaldehyde and 2-hydroxy-3-hydroxymethyl-bromo-benzaldehyde has now been prepared and used for Ni com-plexation. These ligands have monopodal iminic pendent arms and either mono- or dipodal aminic pendent arms and the terminal donors of the pendent arms can be provided by pyridine, imidazole, and tertiary amino groups.1893-1897 Complexes are usually prepared by reaction of the requisite Ni11 salts with the preformed ligand. 

Synthesis of dithieno[2,3-A2,3-,7]thiophene derivatives 122 has been accomplished through the Heck reaction of 3-(4-bromo-2-thienyl)acrylic acid 302 to afford 3-(2,4-thienylene)diacrylic acid 303 which was cyclized with thionyl chloride and a catalytic amount of pyridine to the dichloride 120 in 75% yield (Scheme 56) <2005MOL279>. 

A simple two-step synthesis of 5H-alkyl-2-phenyloxazol-4-ones has been reported by Trost and coworkers (Scheme 6.209) [377]. a-Bromo acid halides were condensed with benzamide in the presence of pyridine base at 60 °C to form the corresponding imides. Microwave irradiation of the imide intermediates in N,N-dimethylacetamide (DMA) containing sodium fluoride at 180 °C for 10 min provided the desired 5H-alkyl-2-phenyloxazol-4-ones (oxalactims) in yields of 44—82%. This class of heterocycles served as excellent precursors for the asymmetric synthesis of a-hydroxycar-boxylic acid derivatives [377]. 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

A recent method for the synthesis of the indolizine skeleton is represented by a three-component reaction between a-bromo ketones 16, pyridine 17, and ethyl propiolate or diethyl acetylenedicarboxylate. These three reagents, under microwave irradiation and catalysis by basic alumina, afforded a good variety of 3-aroyl indolizines 18 <20030L435> (Scheme 4). 

B. Kuhnast, B. Lagnel - de Bruin, F. Hinnen, B. Tavitian, F. Dolle, Design and synthesis of a new [ F]fluoropyridine-based haloacetamide reagent for the labeling of oligonucleotides 2-Bromo-N-[3-(2-[ F]fluoro-pyridin-3-yloxy)-propyl]-acetamide, Bio-conj. Chem. 15 (2004) 617-627. 

Several of the methods of synthesis of 2,2 -bipyridines have their counterpart in the preparation of 4,4 -bipyridine. The Ullmann reaction has been used to prepare 4,4 -bipyridine. Thus 4-halogenated pyridines afford 4,4 -bipyridine. Dehalogenation and dimerization of 4-bromopyridine may be accomplished too with hydrazine and alkali at 65°C in the presence of a palladium catalyst, whereas 4-chloropyridine is converted to 4,4 -bipyridine in 46% yield by reaction with alkaline sodium formate in the presence of palladium on charcoal and a surfactant. Several extensions of the Ullmann reaction have recently been reported, especially for the synthesis of substituted 4,4 -bipyridines. Thus 4-iodo-2-methylpyridine gives 2,2 -dimethyl-4,4 -bipyridine, 3-nitro-4-chloropyridine affords 3,3 -dinitro-4,4 -bipyridine, 4-bromo- or 4-iodotetrafluoropyridine gives octafluoro-4,4 -bipyridine, and 4-iodo- or 4-bromotetrachloropyridine gives octachloro-4,4 -bipyridine. Related syntheses have been de-... 

Chloro-3-hydroxypyridine is a readily available starting point for the synthesis of furo[2,3- ]pyridines via iodina-tion followed by a palladium cross-coupling reaction with alkynes to afford alkynylpyridines, 107. Cyclization of compound 107 leads to furo[2,3- ]pyridine products <1998JME1357, 1998JOC7851 Similarly, reaction of 5-bromo-... 

The synthesis of pyrazolo[3,4-. ]pyridines can be achieved by reaction of 2,6-dichloro-3-lithiopyridine with 5-bromo-2-methoxybenzaldehyde 138 to provide the alcohol, which after Jones oxidation gave ketone 139. Treatment of the ketone with hydrazine furnished the desired pyrazolo[3,4-3]pyridine 140 (Scheme 8) <2006BML262>. 

The procedure described here is by far the most efficient synthesis of terpyridine. Previous preparations include the dehydrogenation of pyridine with ferric chloride, the Ullman reaction of 2-bromopyrid1ne and 2,6-dibromopyridine,5 the action of copper on 2-bromopyridine and 6-bromo-2,2 -... 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

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